Methods for preparing nitrogen substituted amino-5,6,7,8-tetrahydronaphthols have been disclosed in the following documents.
U.S. Pat. No. 4,410,519 (publication date: Oct. 18, 1983) discloses a reaction, by which the amino group of amino-5,6,7,8-tetrahydronaphthol is alkylated while forming acidic by-products (e.g., ZH). The reaction is represented below, in which R4 is alkyl containing 1-4 carbon atoms. The alkylating agent is represented as R3-A-Z, wherein A is —(CH2)n-, n is an integer ranging from 1 to 5; and Z is a leaving group such as alkyl sulfonyloxy or aryl sulfonyloxy. A base may be optionally present.

U.S. Pat. No. 5,382,596 (publication date: Jan. 17, 1995) discloses a reaction as followed in the presence of a base (i.e., a tertiary amine); wherein R4 is a straight alkyl chain containing 1-3 carbon atoms or cyclopropyl methyl; R6 is —(CH2)n-R3, n is an integer ranging from 1 to 4, and R3 is alkoxy, cycloalkoxy or a cyclic ether.

WO 01/38321 discloses the following reaction, in which a base used in the reaction is an alkali carbonate or a bicarbonate, the amount of which is less than 1.9 times by mole as compare to the starting material; R1 is OA; R2 is H or OA, in which A is H, a straight or branched alkyl containing 1-3 carbon atoms; R3 is alkoxy, cycloalkoxy, optionally substituted phenyl, 3-pyridyl or 4-pyridyl; n is an integer ranging from 1 to 5; and Z is a leaving group.

The bases used in the above reactions may only neutralize the acidic by-products generated in the alkylation reactions. However, because the reactions generally need to be carried out at a high temperature for a long time, the starting material containing the phenolic hydroxyl moiety may be easily oxidized to form a number of additional by-products. Therefore, the above reactions not only necessitate multiple purification process steps, but also decrease the reaction yield.
In WO 01/38321, by reducing the amount of the alkali carbonate, plenty of purification steps may be avoided, and the side reactions may be reduced. However, an increased amount of the alkylating agent may be needed to improve the yield of the target product, thus greatly increasing the production cost, and significantly reducing the yield in the large scale production, rendering it unsuitable for industrial productions.